A Novel Vestibular Approach for Gene Transfer into the Inner EarPraetorius M. · Knipper M. · Schick B. · Tan J. · Limberger A. · Carnicero E. · Alonso M.T. · Schimmang T.
aDepartment of Otorhinolaryngology, University Hospitals of the Saarland, Homburg/Saar, bMolecular Neurobiology, Tübingen Hearing Research Centre, University of Tübingen, and cCentre for Molecular Neurobiology Hamburg, University of Hamburg, Germany; dInstituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Cientificas, Departamento de Bioquímica, Biología Molecular y Fisiología, Facultad de Medicina, Valladolid, Spain
The aim of gene transfer to the cochlea and vestibular organ is to protect the inner ear from different disorders. Although various vectors for gene delivery have been used with some success, there remains a need for a reliable transfer of genes into the inner ear without damaging cochlear function. Here, we have tested a novel application method for gene transfer into the rat inner ear in vivo using herpes simplex virus type-1(HSV-1)-based amplicon vectors. Our goal was to find an entry route into the inner ear that leaves its function intact. Besides other non-invasive and invasive application techniques, we applied the viral vector via injection through a small opening of the utriculus. Using this method, efficient β-galactosidase reporter gene expression was achieved in nearly all neurons in the vestibulum and cochlea, without functional hearing deficits. At the time point of maximal expression 5 days after injection, β-galactosidase activity was also observed in axonal fibres and synaptic endings close to inner and outer hair cells. Our results thus describe an efficient and reliable protocol for short-term expression of potential therapeutic genes in the neuronal compartment of the inner ear.
Dr. M. Knipper
Hearing Research Centre Tübingen, Molecular Neurobiology
University of Tübingen, Elfriede-Aulhornstrasse 5
D–72076 Tübingen (Germany)
Tel. +49 7071 2988244, Fax +49 7071 294950, E-Mail Marlies.Knipper@uni-tuebingen.de
Received: Received: September 3, 2001
Accepted after revision: April 11, 2002
Number of Figures : 7, Number of Tables : 1, Number of References : 32
Audiology & Neuro-Otology (Basic Research and Clinical Applications)
Vol. 7, No. 6, Year 2002 (Cover Date: November-December 2002)
Journal Editor: Manfried Hoke, Münster, Germany
ISSN: 1420–3030 (print), 1421–9700 (Online)
For additional information: http://www.karger.com/journals/aud